“The FDA’s clearance of our IND for AMT-130 is a significant milestone for Huntington’s disease patients and an important event in the field of gene therapy,” Matt Kapusta, CEO at uniQure said in a press release.
AMT-130 is an experimental gene therapy that works by inhibiting the production of the mutated or altered form of the huntingtin protein. It does this by carrying a small molecule, called microRNA, that binds to the messenger molecule carrying instructions for the production of the huntingtin protein to destroy it. As a result, AMT-130 lowers the levels of the defective huntingtin protein.
The therapy is carried by a special class of virus — adeno-associated virus (AAV) — that is unable to trigger an infection, thereby working solely as a vehicle to deliver AMT-130 to nerve cells. As cells are invaded and internalize the virus, they also internalize AMT-130. Once inside the cell, the miRNA is capable of binding to the existing messenger RNA molecule for the huntingtin protein.
“We expect that AMT-130 will be the first one-time administered AAV gene therapy to enter clinical testing for the treatment of Huntington’s disease, a devastating neurodegenerative disorder for which there is no approved disease-modifying treatment,” Kapusta said.
The trial will be performed at several clinical sites in the U.S. and will assign Huntington’s patients randomly to escalating doses of a one-time treatment of AMT-130. The aim is to assess the therapy’s safety, tolerability and effectiveness. The company expects to begin dosing patients in the second half of this year.
Previous preclinical studies have shown that AMT-130 improves motor coordination and survival in mouse models of Huntington’s disease. These results were followed by a report showing the therapy was able to penetrate the brain and spinal cord following direct injection in a non-human primate.
The therapy received FDA’s orphan drug designation in October 2017.
“AMT-130 also represents the first clinical-stage AAV-based therapy specifically designed to silence an abnormal gene in the brain with a single administration,” Kapusta said.
“This achievement is a major milestone for uniQure’s research organization, who have dedicated years of effort with the hope we can one day offer treatment for the many patients waiting generations for an effective therapy,” he added.